Journal: Archives of Toxicology

Article Title: Ferroptosis regulation through Nrf2 and implications for neurodegenerative diseases

doi: 10.1007/s00204-023-03660-8

Figure Lengend Snippet: Characterization of ferroptosis in neurodegenerative diseases (NDs) pathological conditions. There exists a significant correlation between ferroptosis and NDs. Ferroptosis contributes to the advancement of NDs, whereas the expression of Nrf2 and its transcriptionally regulated peptides (GSH, GPX4) decreases with aging. In contrast to the impairment of the antioxidant system, heightened levels of reactive oxygen species (ROS) and increased lipid peroxidation, combined with brain iron deposition, induce ferroptosis. Ferroptosis results in alterations in mitochondrial morphology, neuronal damage and eventual cell death. Drawing by Inkscape

Article Snippet: MitoQ , Radical Trapping Antioxidant (RTA, Targets mitochondrial ROS scavenging → rescues mitochondrial integrity and function) , Oxidative cell death , RSL3-treated neuronal HT22 cells , Mitochondrial ROS, lipid peroxidation↓ , Jelinek et al. ( ) .

Techniques: Expressing

Journal: Archives of Toxicology

Article Title: Ferroptosis regulation through Nrf2 and implications for neurodegenerative diseases

doi: 10.1007/s00204-023-03660-8

Figure Lengend Snippet: Nrf2-regulated iron death mechanisms in neurodegenerative diseases. a Blood–brain barrier (BBB), astrocytes, and neurons. Brain capillary endothelial cells (BCECs) safeguard the function of the BBB. Astrocytes on the abluminal surface of BCECs promote brain iron uptake. Astrocytes are primarily responsible for releasing iron into neurons while attenuating iron toxicity. b the transcytosis model. After Fe 3+ entering the blood circulation forms a complex (holo-Tf) with transferrin (Tf), it binds to TfR1 on the surface of brain microvascular endothelial cells (BMECs), and then the Tf–TfR1 complex enters BMECs through clathrin-mediated endocytosis. One of the two models of iron import across BCEC—the transcytosis model. Holo-Tf is transported directly by vesicles to extraluminal sites for release into the brain. c Nrf2 in astrocytes activates non-cell-autonomous protection of nearby neurons and alleviates oxidative stress (OS) by mediating antioxidant responses. GSH produced in the brain via activated Nrf2 pathway is predominantly derived from astrocytes, whose neuroprotective function depends on the transport of GSH precursors from astrocytes to motor neurons. d Regulation of iron in neurons and mechanisms of Nrf2-regulated ferroptosis in neurodegenerative diseases. The key components of ferroptosis are the lipid and antioxidant systems, as well as iron metabolism. metabolism of iron: The Tf–TfR1 complex carrying Fe 3+ is endocytosed into neurons, Fe 3+ is separated from Tf, and then reduced to Fe 2+ by six transmembrane epithelial antigen-prostate 3 (STEAP3), and Fe 2+ is pumped into the cytoplasm through divalent metal transporter 1 (DMT1), which is also a classic model of iron import across BCEC. Alternatively, Fe 3+ reduced by cellular prion protein (PrPC) is transported into neurons by DMT1. In addition, solute carrier family 39 member 14 (SLC39A14) can also transport Fe 2+ into the cell. Intracellular iron can be stored in two forms: as Fe 3+ stored in ferritin or as active unbound iron called the labile iron pool (LIP). Poly-(rC)-binding protein1/2 (PCBP1/2) are in charge of transferring the iron to ferritin. In some cases, nuclear receptor coactivator 4 (NCOA4) mediates ferritin autophagy, releasing iron. Heme oxygenase 1 (HO1) catalyzes the degradation of heme and can also release Fe 2+ . With the aid of amyloid precursor protein (APP), which is transmitted by soluble tau protein to stabilize FPN1, elevated Fe 2+ can be expelled through Ferroportin1 (FPN1)/copper cyanine (Cp) or FPN1/hephaestin (Heph). Through the IRP–IRE interaction, iron can, when overloaded, increase the expression of ferritin, FPN1, and APP, while blocking the ordinary function of furin, upregulating secretase, and speeding up the deposition of Aβ. By the Fenton reaction, excessive Fe 2+ produces ROS and encourages the oxidation of PUFA on the membranes of cells (PE-PUFA), and finally triggers ferroptosis. Lipid metabolism: Lysophospholipid acyltransferase 3 (LPCAT3), long-chain fatty acid CoA ligase 4 (ACSL4), and other enzyme-sensitize membrane lipids to lipid peroxidation, which, catalyzed by lipoxygenases (LOX), accumulates PUFA-OOH, triggering ferroptosis. Antioxidant system: GSH–GPX4 axis in cytoplasm and mitochondria, ferroptosis suppressor protein 1 (FSP1)–CoQ10 axis in plasma membrane, dihydroorotate dehydrogenase (DHODH)–CoQ 10 H 2 , and GTP cyclohydrolase1–tetrahydrobiopterin (GCH1–BH 4 ) axis in mitochondria. Mitochondrial PTEN-inducible putative kinase 1 (PINK1) expression is regulated by Nrf2 under OS conditions. Keap1–Nrf2–ARE axis: Under OS conditions, Keap1 releases Nrf2, and the increase of Nrf2 levels in the cytoplasm increases its nuclear translocation. Upon nuclear import, Nrf2 forms a heterodimer with the small muscular aponeurotic fibrosarcoma (Maf) protein, enabling Nrf2 to bind to AREs in the upstream promoter regions of a variety of target genes, leading to their transcriptional activation. Drawing by Inkscape

Article Snippet: MitoQ , Radical Trapping Antioxidant (RTA, Targets mitochondrial ROS scavenging → rescues mitochondrial integrity and function) , Oxidative cell death , RSL3-treated neuronal HT22 cells , Mitochondrial ROS, lipid peroxidation↓ , Jelinek et al. ( ) .

Techniques: Produced, Derivative Assay, Binding Assay, Transferring, Expressing, Blocking Assay, Membrane, Clinical Proteomics, Translocation Assay, Activation Assay

Journal: Archives of Toxicology

Article Title: Ferroptosis regulation through Nrf2 and implications for neurodegenerative diseases

doi: 10.1007/s00204-023-03660-8

Figure Lengend Snippet: Signaling molecules associated with ferroptosis and regulated by Nrf2

Article Snippet: MitoQ , Radical Trapping Antioxidant (RTA, Targets mitochondrial ROS scavenging → rescues mitochondrial integrity and function) , Oxidative cell death , RSL3-treated neuronal HT22 cells , Mitochondrial ROS, lipid peroxidation↓ , Jelinek et al. ( ) .

Techniques: Binding Assay, Functional Assay, Clinical Proteomics, Membrane

Journal: Cancer Immunology, Immunotherapy : CII

Article Title: Antibody responses to galectin-8, TARP and TRAP1 in prostate cancer patients treated with a GM-CSF-secreting cellular immunotherapy

doi: 10.1007/s00262-010-0858-5

Figure Lengend Snippet: Anti-human galectin-8, TARP and TRAP1 antibodies in patients treated with GVAX immunotherapy for prostate cancer. A longitudinal analysis of humoral reactivity to human galectin-8 (upper panels), TARP (middle panels) and TRAP1 (lower panels) in two G-0010 patients: 057 (a) and 202 (b). Serum samples at representative time points over the course of immunotherapy treatment were diluted 1:100 and incubated with 200 ng of the target antigen in an ELISA assay. An anti-human pan-IgG secondary antibody was used for detection. Arrows denote immunization with irradiated GM-CSF-secreting tumor cells

Article Snippet: Full-length LGALS8 , TARP and TRAP1 cDNAs were obtained from Origene (Rockville, MD, USA), PCR cloned with a C-terminus Flag-tag and transfected into 293 cells for protein production.

Techniques: Incubation, Enzyme-linked Immunosorbent Assay, Irradiation

Journal: Cancer Immunology, Immunotherapy : CII

Article Title: Antibody responses to galectin-8, TARP and TRAP1 in prostate cancer patients treated with a GM-CSF-secreting cellular immunotherapy

doi: 10.1007/s00262-010-0858-5

Figure Lengend Snippet: RNA encoding the TARP and TRAP1 antigens shows enhanced expression in prostate cancer. RNA was extracted from normal (N = 8) and cancerous (N = 40) prostate tissue samples, cDNA was synthesized and then normalized for ACTB expression. Q-PCR primer and probe sets specific for LGALS8 (a), TARP (b), TRAP1 (c) and ACTB (d; control) were used to determine RNA transcript levels. C t denotes cycle threshold. A decrease in C t represents an increase in RNA transcript

Article Snippet: Full-length LGALS8 , TARP and TRAP1 cDNAs were obtained from Origene (Rockville, MD, USA), PCR cloned with a C-terminus Flag-tag and transfected into 293 cells for protein production.

Techniques: Expressing, Synthesized, Control

Journal: Cancer Immunology, Immunotherapy : CII

Article Title: Antibody responses to galectin-8, TARP and TRAP1 in prostate cancer patients treated with a GM-CSF-secreting cellular immunotherapy

doi: 10.1007/s00262-010-0858-5

Figure Lengend Snippet: Kaplan–Meier estimates of overall survival in G-9803/G-0010 mCRPC patients with (solid lines) or without (dashed lines) an induced antibody response to galectin-8 (a), TARP (b) or TRAP1 (c)

Article Snippet: Full-length LGALS8 , TARP and TRAP1 cDNAs were obtained from Origene (Rockville, MD, USA), PCR cloned with a C-terminus Flag-tag and transfected into 293 cells for protein production.

Techniques:

Journal: Cancer Immunology, Immunotherapy : CII

Article Title: Antibody responses to galectin-8, TARP and TRAP1 in prostate cancer patients treated with a GM-CSF-secreting cellular immunotherapy

doi: 10.1007/s00262-010-0858-5

Figure Lengend Snippet: Humoral responses to TARP are observed in CRPC patients before immunotherapy treatment. Comparison of antibody reactivity (OD at 450 nm) between normal (N = 25) and CRPC patients before the initiation of immunotherapy treatment (N = 60) to the galectin-8 (a), TARP (b) and TRAP1 (c) antigens. Serum samples were diluted 1:100 and incubated with 200 ng of the target antigen in an ELISA assay using an anti-human pan-IgG secondary antibody for detection

Article Snippet: Full-length LGALS8 , TARP and TRAP1 cDNAs were obtained from Origene (Rockville, MD, USA), PCR cloned with a C-terminus Flag-tag and transfected into 293 cells for protein production.

Techniques: Comparison, Incubation, Enzyme-linked Immunosorbent Assay

Journal: Cancer Immunology, Immunotherapy : CII

Article Title: Antibody responses to galectin-8, TARP and TRAP1 in prostate cancer patients treated with a GM-CSF-secreting cellular immunotherapy

doi: 10.1007/s00262-010-0858-5

Figure Lengend Snippet: TARP and TRAP1 protein is over-expressed in prostate cancer. Representative photomicrographs of normal prostate (a, c) and prostate adenocarcinoma (b, d) tissue stained with an anti-TARP (upper panels) or anti-TRAP1 (lower panels) antibody. Original magnifications: ×5 (main-panel) and ×40 (sub-panel). Black boxed area (×5 magnification) indicates the area examined under higher magnification (×40) presented below. e, f TARP and TRAP1 RNA expression in a panel of cell lines as evaluated by quantitative PCR. RNA was extracted from PC-3, LNCaP, 293, K-562 and HeLa cells, cDNA synthesized and expression determined using gene specific Q-PCR primer and probe sets. C t denotes cycle threshold. A decrease in C t represents an increase in RNA transcript

Article Snippet: Full-length LGALS8 , TARP and TRAP1 cDNAs were obtained from Origene (Rockville, MD, USA), PCR cloned with a C-terminus Flag-tag and transfected into 293 cells for protein production.

Techniques: Staining, RNA Expression, Real-time Polymerase Chain Reaction, Synthesized, Expressing

Journal: Cancer Immunology, Immunotherapy : CII

Article Title: Antibody responses to galectin-8, TARP and TRAP1 in prostate cancer patients treated with a GM-CSF-secreting cellular immunotherapy

doi: 10.1007/s00262-010-0858-5

Figure Lengend Snippet: Target antigens in immunotherapy treated patients ( N = 13) identified by autoantibody profiling of patients serum using protein microarray analysis

Article Snippet: Full-length LGALS8 , TARP and TRAP1 cDNAs were obtained from Origene (Rockville, MD, USA), PCR cloned with a C-terminus Flag-tag and transfected into 293 cells for protein production.

Techniques: Microarray, Binding Assay

Journal: Journal of Immunology Research

Article Title: Endoplasmic Reticulum Stress-Related Signature for Predicting Prognosis and Immune Features in Hepatocellular Carcinoma

doi: 10.1155/2022/1366508

Figure Lengend Snippet: Validation of this feature in clinical samples. (a) Expression levels of mRNA molecules in our risk model. (b) ROC curve. (c, d) SSR2 was associated with poor progression. (e) The protein expression of SSR2 was overexpressed in HCC compared to normal tissues.

Article Snippet: SSR2 antibody was obtained from Proteintech (China).

Techniques: Biomarker Discovery, Expressing